The primary objective of this mentored career development award in patient-oriented research is for the candidate, Dr. Wynnis Tom, to acquire the skills and expertise to become an independent investigator leading clinical and genetic studies on pediatric inflammatory skin diseases, particularly psoriasis. Under the direction of Drs. Jane Burns and Kelly Frazer, the candidate has constructed a focused training program that includes intensive coursework and research training. The didactic component will include formal coursework on human genetics and genomics, clinical and translational research, biostatistics, and ethics, along with weekly seminars, regular face-to-face mentor meetings and participation in weekly laboratory meetings. In addition, this career development program will benefit from the oversight of a carefully selected Advisory Committee of senior research scientists with expertise in genetic analysis of complex human diseases, recruitment and study of large pediatric and parent cohorts, and clinical and translational research. The research for this proposal consists of a comparative study of gene expression profiles in children and adults with psoriasis and a prospective cohort study that will investigate single nucleotide polymorphisms (SNPs) in candidate susceptibility genes as prognostic markers for pediatric psoriasis patients. The three specific aims are: 1) To compare expression in lesional and unaffected or normal skin obtained from healthy children, children with psoriasis, adults with childhood-onset psoriasis, and adults with adult-onset psoriasis; 2) To analyze SNPs in 14 genes previously associated with adult psoriasis and SNPs in 14 genes in the calcineurin/NFAT pathway in pediatric psoriasis subjects and their biological parents; and 3) To stratify genetic analysis by subject response to therapy and disease severity. The proposed studies will reveal how molecular pathways and genetic influences may be similar or different in pediatric psoriasis patients as compared to adults. Results may identify additional targets for drug development and predictors of disease course and response to pharmacotherapy in young patients suffering from psoriasis.